Bromomethyl 3-methoxyphenyl ketone → Azemiglitazone

HRID 1427540Notes

Reaction equation

HRID 1427540 reaction equation
[OH:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][CH:7]2[S:11][C:10](=[O:12])[NH:9][C:8]2=[O:13])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Br[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=1)=[O:25]>CS(C)=O>[CH3:33][O:32][C:28]1[CH:27]=[C:26]([C:24](=[O:25])[CH2:23][O:1][C:2]2[CH:15]=[CH:14][C:5]([CH2:6][CH:7]3[S:11][C:10](=[O:12])[NH:9][C:8]3=[O:13])=[CH:4][CH:3]=2)[CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 101294Bromomethyl 3-methoxyphenyl ketoneHCID 101983975-(4-Hydroxybenzyl)thiazolidine-2,4-dioneHCID 23665647Potassium tert-butoxide

Product 1

HCID 25230266AzemiglitazoneYield 47.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirring solution of 5-(4-hydroxybenzyl)thiazolidine-2,4-dione (100 mg, 0.4 mmol) in DMSO (2 ml), potassium tert-butoxide (106 mg, 0.941 mmol) was added. Stirring continued at RT for about 1 hour. 2-Bromo-3′-methoxyacetophenone (100 mg, 0.5 mmol) was then added to the mixture. After 2 hours, LCMS showed that the reaction was complete. The reaction mixture was partitioned between EtOAc and water, and the aqueous phase was extracted with EtOAc. Combined extracts were washed with brine, dried on (Na2SO4), filtered, and evaporated in vacuo. The residue was chromatographed on a small RediSep column eluting with 0-10% acetone/DCM. Fractions containing the product were combined and evaporated in vacuo to afford 70 mg of 5-{4-[2-(3-methoxyphenyl)-2-oxoethoxy]benzyl}-1,3-thiazolidine-2,4-dione as a pale yellow solid. 1H-NMR (DMSO-d6): δ 12.49 (brs, 1H), 7.72(s, 1H), 7.59(m, 1H), 7.53-7.46(m, 4H), 7.24(dd, J=8.2, 2.4 Hz, 1H), 7.10(d, J=8.7 Hz, 2H), 5.66(s, 2H), (3.80(s, 3H). HPLC: 3.969 min., 61 area % @2540 nm; 3.969 min., 62 area % @210 nm. MS (ESI−) for C19H15NO5S m/z 368.4 (M−H)−.

Workup

  1. waitAfter 2 hours
  2. customThe reaction mixture was partitioned between EtOAc and water
  3. extractionthe aqueous phase was extracted with EtOAc
  4. washCombined extracts were washed with brine
  5. dry with materialdried on (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was chromatographed on a small RediSep column
  9. washeluting with 0-10% acetone/DCM
  10. additionFractions containing the product
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-112604b205d94cdf80d44c436f51c291
Source dataset
uspto-grants-2015_01
Patent number
US08933240B2

Reaction notes

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